Antischistosomal drugs usually interfere with the motor activity of the schistosome by direct or indirect interaction with the parasite's musculature. Previous research on the neuromuscular system of the schistosome indicates that this system plays an important role in regulating complex movements by the parasite. Nothing, at present, is known about the mechanical and biophysical properties of the neuromuscular system of the schistosome or how drugs interact with this system. The immediate objective of the proposed study is to elucidate the mechanical and biophysical properties of this parasite's neuromuscular system and determine how drugs interact with this system. This will be accomplished by applying newly developed mechanical and electrophysiological techniques for studying neurobiological processes in small helminths. Once we understand the basic neurobiological processes within this parasite we will analyze the effects of three new antischistosomal drugs. These drugs are unusual compared to other antischistosomal compounds because they all produce a rapid and massive contraction of the schistosome's musculature at low concentrations (10 to the minus 7th power M). Thus, our second major objective will be to elucidate their mode of action and then synthesize and test analogs of these compounds on the neuromuscular system of this parasite to determine the molecular requirements necessary for their antischistosomal action. Our long-term objective will be to identify antischistosomal compounds that will act more selectively (i.e., less toxicity to the host) and effectively upon the neuromuscluar system of the schistosome.